The over-arching theme of this proposal is to train comprehensive imaging scientists in the skills necessary to identify clinically relevant problems; develop instrumentation, sensors, and contrast agents to form images appropriate for the problem; and analyze the resulting imaging data using signal processing, mathematical modeling, visualization, and informatics techniques to improve the prevention, detection, diagnosis, and treatment of human diseases. The breadth of focus spans the full range of physical dimensions from molecular to cellular to tissue to organ. In order for imaging scientists to knowledgeable of the full trajectory from image formation to analysis and decision-making, they must be rained in four core areas: Instrumentation, Devices, and Contrast Agents; Image processing; Modeling and Visualization; and Informatics. We have chosen a solid core curriculum upon which the trainees can build a specialized research career. The faculty comefrom a wide range of research areas: chemistry, biochemistry, engineering, biology, psychology, and clinical medicine. Research spans the full gamut from contrast agent design and cell trafficking measurementsto clinical instrumentation design. All students in the program will be trained in the core concepts of all of these areas. In addition, each student will identify a particular area in which to specialize for his/her doctoral research. For example, this area may be a particular imaging modality or a specialization within imaging informatics. The proposed training program is a two year pre-doctoral portfolio program. A total of twenty students will be trained (4/year). The program includes industrial internships and professional development so that our students will be able to fill a critical niche in imaging science. A novel element of the training program is the integration of quantitative physiological modeling at all scaleswith state-of-the-artimagingscience. Structural imaging changed the practice of clinical medicine in the 1980s. Medicine is poised for a second revolution based on functional imaging, especially at the cellular and molecular level. It is completely feasible to imagine a scenario in which the dynamics of cellular metabolism are measured in vivo and targeted drugs or gene therapies are custom designed to alter or repair intracellular biochemical pathways. We have identified a critical need for imaging scientists to work at this new frontier of medicine. The global program outcome is for our students to acquire the skill set needed to improve healthcare through imaging science.